Efficacy and Safety of Treatment with Methotrexate Versus a Combination of Low Dose of Methotrexate Plus Low Dose of Acitretin in Chronic Plaque Psoriasis: A Randomised Nonblinded Controlled Trial

Abstract Background: Psoriasis is a chronic, inflammatory disease with no cure. Methotrexate (MTX) and acitretin (ACI) are well-established, FDA-approved systemic therapies for chronic plaque psoriasis. However, randomized trials evaluating their combination in fixed low doses are limited due to concerns of additive hepatotoxicity. Aim and Objectives: To assess and compare efficacy and safety of treatment with MTX (0.3 mg/kg/week) versus low-dose MTX (0.15 mg/kg/week) plus low-dose ACI (0.3 mg/kg/day) in patients with chronic plaque psoriasis. Patients and Methods: This was a nonblinded randomized controlled trial. Patients with chronic plaque psoriasis having body surface area (BSA)>10% and psoriasis area severity index (PASI)>10 were randomized into two groups. One group received intramuscular MTX 0.3 mg/kg/week, and the other received intramuscular MTX 0.15 mg/kg/week plus oral ACI 0.3 mg/kg/day. Patients were followed every 2 weeks for first 4 weeks and monthly thereafter till 16 weeks. Results: A total of 134 patients (67 in each group) were analyzed. Baseline BSA and PASI were comparable between groups ( P = 0.54 and P = 0.82, respectively) and showed significant reduction at 16 weeks in both arms ( P = 0.01 and P = 0.04). PASI-75, 90, and 100 at 16 weeks were slightly higher in monotherapy group but not statistically significant on per-protocol or intention-to-treat analyses. Onset of action was significantly earlier in monotherapy group ( P = 0.001). Laboratory and clinical adverse effects between groups were mild and manageable. Limitations: Nonblinded, absence of ACI monotherapy arm, limited study duration, and lack of noninvasive hepatic fibrosis assessment. Conclusion: Low-dose MTX plus ACI is a safe and effective alternative to standard-dose MTX in chronic plaque psoriasis, provided regular monitoring and follow-up are ensured.